Cesium carbonate → Tert-butyl 4-(3-((R)-3-(((S)-3-(tert-butoxy)-3-oxo-1-(4-(2-(tosyloxy)ethoxy)phenyl)propyl)carbamoyl)piperidin-1-YL)-3-oxopropyl)piperidine-1-carboxylate

HRID 526370Notes

Reaction equation

HRID 526370 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24](=[O:42])[NH:25][C@H:26]([C:35]3[CH:40]=[CH:39][C:38]([OH:41])=[CH:37][CH:36]=3)[CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[C:49]1([CH3:72])[CH:54]=[CH:53][C:52]([S:55]([O:58][CH2:59][CH2:60]OS(C2C=CC(C)=CC=2)(=O)=O)(=[O:57])=[O:56])=[CH:51][CH:50]=1>CN(C)C=O>[C:31]([O:30][C:28](=[O:29])[CH2:27][C@H:26]([NH:25][C:24]([C@@H:20]1[CH2:21][CH2:22][CH2:23][N:18]([C:16](=[O:17])[CH2:15][CH2:14][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]2)[CH2:19]1)=[O:42])[C:35]1[CH:40]=[CH:39][C:38]([O:41][CH2:60][CH2:59][O:58][S:55]([C:52]2[CH:53]=[CH:54][C:49]([CH3:72])=[CH:50][CH:51]=2)(=[O:57])=[O:56])=[CH:37][CH:36]=1)([CH3:32])([CH3:33])[CH3:34]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 228289Ethylene glycol ditosylateHCID 712589314-(3-{(R)-3-[(S)-2-tert-butoxycarbonyl-1-(4-hydroxy-phenyl)-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 89407760Tert-butyl 4-(3-((R)-3-(((S)-3-(tert-butoxy)-3-oxo-1-(4-(2-(tosyloxy)ethoxy)phenyl)propyl)carbamoyl)piperidin-1-YL)-3-oxopropyl)piperidine-1-carboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

270.0 mg (0.46 mmol) 4-(3-{(R)-3-[(S)-2-tert-butoxycarbonyl-1-(4-hydroxy-phenyl)-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester were dissolved in 17.7 ml N,N-dimethylformamide. 449 mg (1.38 mmol) cesium carbonate and 255.3 mg (0.69 mmol) ethylene glycol bis-p-toluenesulfonate were added. The mixture was stirred at room temperature for 20 hours and concentrated. The remainder was taken up with saturated ammonium chloride solution and ethyl acetate. The aqueous phase was extracted with 3×20 ml ethyl acetate. The extracts were dried over sodium sulfate and concentrated. Chromatography over 10 g silica gel (dichloromethane/ethanol 100/0-90/10) gave 227 mg (63%) tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[4-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate which were purified by HPLC:

Workup

  1. concentrationconcentrated
  2. extractionThe aqueous phase was extracted with 3×20 ml ethyl acetate
  3. dry with materialThe extracts were dried over sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-11e8e2ec4de6481b9aebbf7155573a1b
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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